Patent GB-794775-A (GB)
Title: Process for the production of acyl derivatives of 5.6-dihydrobenzo (c) cinnoline
IPC: C07D487/04
Filed: 1956-02-16
Abstract: 794,775. Substituted benzo (c) cinnolines. GEIGY AKT.-GES. J. R. Feb. 16, 1956 [Feb. 16, 1955], No. 4809/56. Class 2 (3). The invention comprises acyl derivatives of 5,6-dihydro-benzo (c) cinnoline of the general formula: or tautomeric enol forms thereof, wherein R represents hydrogen or an aliphatic, cycloaliphatic, aromatic, araliphatic, or heterocyclic radical bound to the rest of the molecule by a carbon atom, and R 1  and R 2  represent hydrogen, halogen atoms or methyl groups, and the preparation thereof by condensing a reactive functional derivative of a malonic acid of the general formula: wherein R has the above significance, with an N,N<SP>1</SP>-di-metal compound, e.g. the disodium, dipotassium, dilithiurn or dimagnesium com- .pound, of a 5,6-dihydro-benzo (c) cinnoline of the general formula: wherein R 1  and R 2  have the above significance, in the absence of an acid binding or alkaline condensing agent, or by reacting a 5,6-dihydrobenzo (c) cinnoline of the general formula: wherein R 1  and R 2  have the above significance, or an N-acyl derivative thereof, with a malonic acid diester of the general formula: wherein X represents the residue of a hydroxyl compound, in the presence of an alkaline condensing agent, or with a malonic acid derivative of the general formula : wherein R has the above significance and Y represents a chlorine or bromine atom or an acyloxy radical, in the presence of an acid binding agent, or with a malonic acid derivative of the general formula: wherein R, X and Y have the above significance in the cold to form an N-(α-carbalkoxyacyl)-dihydrobenzocinnoline of the general formula : wherein R, R 1'  R 2  and X have the above significance, which is then reacted with an alkaline condensing agent, or in the case where R is other than hydrogen, by reacting, an N,Nlmalonyl-dihydrobenzbcinnoline of the general formula: wherein R 1  and R 2  have the above significance, with an organic oxo compound of the general formula R<SP>1</SP> = O, wherein R<SP>1</SP> represents the geminate divalent radical corresponding to the R radical and has, therefore, one hydrogen atom less, and simultaneously or subsequently reacting the resulting N,N<SP>1</SP>-(unsaturated substituted malonyl) - 5,6 - dihydro - benzo (c) cinnoline of the general formula: with catalytically activated hydrogen, e.g. hydrogen in the presence of hydrogen activated noble metal catalysts or Raney nickel. Suitable alkaline condensing agents are alkali metals and compounds thereof such as alcoholates, amides and hydrides. Suitable acid binding agents are tertiary organic bases such as pyridine, dimethylaniline and triethyl- and tributylamine. Suitable malonic acid diesters and substituted malonic acid diesters mentioned are the dimethyl and diethyl esters of malonic acid and of the following monosubstituted malonic acids: methyl, ethyl-, n- and iso-propyl-, n-, iso-, sec.- and tert.-butyl-, n- and iso-amyl-, n-hexyl-, nheptyl-, n-octyl-, #-ethylhexyl-, decyl-, dodecyl-, cetyl-, octadecyl-, allyl-, crotyl-, methallyl-, octadecenyl-, #-methoxyethyl-, #-ethoxyethyl-, # - n - butoxyethyl -, # - methylmercaptoethyl-, # - isopropylmercaptoethyl -, γ - methylmercaptopropyl -, # - dimethylaminoethyl -, #- diethylaminoethyl -, cyclopentyl -, cyclohexyl-, cycloheptyl -, cyclohexenyl -, 2,5 - endomethylene - #<SP>3</SP> - cyclohexenyl -, 2,5 - endomethylene- #<SP>3</SP> - cyclohexenylmethyl -, benzyl -, p - chlorobenzyl -, m,p dichlorobenzyl -, p - bromobenzyl -, p - methoxybenzyl -, # - phenylethyl-, y - phenylpropyl -, cinnamyl -, p - phenoxyethyl -, p - phenylmercaptoethyl -, y - phenylmercaptopropyl -, phenyl -, p - chlorophenyl-, m,p dimethylphenyl -, p - methoxyphenyl, furyl - (2) -, furfuryl - (2) -, tetrahydrofurfuryl- (2) -, # - tetrahydropyraryloxy - (2) - butyl -, γ,γ - ethylenedioxybutyl -, thienyl - (2)-, thenyl -, pyridyl - (2) -, pyridyl - (4) -, α- picolyl -, γ - picolyl -, # - pyridyl - (4) - ethyl-, # - pyrrolidinoethyl -, # - piperidinoethyl-, indolyl - (3) - methyl -, 1 - methyl - indolyl - (3)- methyl -, quinolyl - (2) - methyl -, quinolyl - (4)- methyl -, # - morpholinoethyl -, # - (4 - methylpiperazino)ethyl -, γ - pyridyl - (2) - mercaptopropyl - and γ - benthiazolyl - (2) - mercaptopropyl - malonic acids. Examples of 5,6 - dihydro-benzo (c) cinnoline which may be used as reactants are 5,6-dihydro-benzo (c) cinnolines, 1,10 - dimethyl - 5,6 - dihydrobenzo (c) cinnoline, 2,9 - dimethyl - 5,6 - dihydro - benzo (c) cinnoline, 3,8 - dimethyl - 5,6 - dihydrobenzo (c) cinnoline 3,8 - dichloro - 5,6 - dihydrobenzo (c) cinnoline and 3-bromo-5,6-dihydrobenzo (c) cinnoline. Suitable oxo compounds of the general formula R<SP>1</SP> = O mentioned are acetaldehyde, butyraldehyde, enanthaldehyde, crotonaldehyde, # - methoxypropionaldehyde, benzaldehyde, phenyl acetaldehyde, #-phenyl propionaldehyde, cinnamic aldehyde, furfural, nicotinaldehyde, isonicotinaldehyde, acetone, butanone, cyclopentanone, cyclohexanone, cycloheptanone and acetophenone. A number of detailed examples are given, the reactants used being included in the lists referred to above.